We continue to study inborn errors of metabolism with special emphasis on nephropathic cystinosis. Basic research into this disorder has been directed toward characterizing the normal lysosomal membrane's cystine transport system and comparing it with the system we have demonstrated to be defective in cystinosis. The intact system is stimulated by divalent cations such as magnesium at pH 5.5, and does not appear to require proton-pump mediated acidification for normal functioning. However, cystine storage in I-cell lysosomes suggests that the lysosomal cystine carrier may require either a mannose-6-phosphate recognition marker for placement in the lysosomal membrane, or processing by hydrolases deficient in I-cell disease. Clinical investigations into cystinosis have revealed a significant hypohydrosis in cystinotic children and a substantial deficiency of plasma free carnitine in all patients due to failure of the kidney to reabsorb carnitine. We have shown that cystinotics receiving cysteamine as a cystine-depleting agent exhibit an impaired prolactin response to thyroid releasing factor, and we have described nephropathic cystinosis and Fabry disease in a single sibship under our care. Pantethine has been investigated as a cystine depleting agent in cystinosis and patient recruitment has begun for a study of betaine's effects on bone density in homocystinuria. The transport of sialic acid across the lysosomal membranes of normal and sialic acid storage disease fibroblasts is being actively pursued.